Isotetrandrine
(Synonyms: 异汉防己甲素) 目录号 : GC39801
Isotetrandrine 是 S. acutum 中的活性成分。
Cas No.:477-57-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Isotetrandrine is a bioactive component in S. acutum[1].
[1]. Kim, Ji Hee et al. UHPLC Separation of Structurally Diverse Markers in Fangchi Species. (2013).
| Cas No. | 477-57-6 | SDF | |
| 别名 | 异汉防己甲素 | ||
| Canonical SMILES | COC1=C(O2)C3=C(C=C1OC)CCN(C)[C@]3([H])CC4=CC=C(OC)C(OC5=CC=C(C=C5)C[C@@]6([H])C7=C(CCN6C)C=C(OC)C2=C7)=C4 | ||
| 分子式 | C38H42N2O6 | 分子量 | 622.75 |
| 溶解度 | Soluble in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6058 mL | 8.0289 mL | 16.0578 mL |
| 5 mM | 0.3212 mL | 1.6058 mL | 3.2116 mL |
| 10 mM | 0.1606 mL | 0.8029 mL | 1.6058 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Isotetrandrine ameliorates tert-butyl hydroperoxide-induced oxidative stress through upregulation of heme oxygenase-1 expression
Exp Biol Med (Maywood) 2016 Aug;241(14):1568-76.PMID:27190261DOI:10.1177/1535370216647122.
1R, 1'S-isotetrandrine, a naturally occurring plant alkaloid found in Mahonia of Berberidaceae, possesses anti-inflammatory, antibacterial, and antiviral properties, but the antioxidative activity and mechanism action remain unclear. In this study, we demonstrated the antioxidative effect and mechanism of 1R, 1'S-isotetrandrine against tert-butyl hydroperoxide-induced oxidative damage in HepG2 cells. We found that 1R, 1'S-isotetrandrine suppressed cytotoxicity, reactive oxygen species generation, and glutathione depletion. Additionally, our study confirmed that 1R, 1'S-isotetrandrine significantly increased the antioxidant enzyme heme oxygenase-1 expression and nuclear translocation of factor-erythroid 2 p45-related factor 2 (Nrf2). Specifically, the nuclear translocation of Nrf2 induced by 1R, 1'S-isotetrandrine was associated with Nrf2 negative regulatory protein Keap1 inactivation and phosphorylation of both extracellular signal-regulated protein kinase and c-Jun NH2-terminal kinase. Preincubation with thiol-reducing agents reduced 1R, 1'S-isotetrandrine-induced heme oxygenase-1 expression, and treatment with either extracellular signal-regulated protein kinase or c-Jun NH2-terminal kinase inhibitors attenuated the levels of 1R, 1'S-isotetrandrine-induced Nrf2 activation and heme oxygenase-1 expression. Furthermore, the cytoprotective effect of 1R, 1'S-isotetrandrine was abolished by heme oxygenase-1, extracellular signal-regulated protein kinase, and c-Jun NH2-terminal kinase inhibitors. These results indicated that the 1R, 1'S-isotetrandrine ameliorated tert-butyl hydroperoxide-induced oxidative damage through upregulation of heme oxygenase-1 expression by the dissociation of Nrf2 from Nrf2-Keap1 complex via extracellular signal-regulated protein kinase and c-Jun NH2-terminal kinase activation and Keap1 inactivation.
Absolute configuration of tetrandrine and Isotetrandrine influences their anti-proliferation effects in human T cells via different regulation of NF-κB
Z Naturforsch C J Biosci 2020 Oct 30;76(1-2):21-25.PMID:33119545DOI:10.1515/znc-2020-0064.
Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-κB. Chemically, Isotetrandrine differs from tetrandrine only in the stereochemistry at the chiral centers. The present study aimed to compare their anti-proliferation effects on human T cells with a focus on NF-κB. The IC50 values of tetrandrine against MOLT-4 cells, MOLT-4/DNR cells, and concanavalin A-activated peripheral blood mononuclear cells of healthy subjects and dialysis patients were 4.43 ± 0.22, 3.62 ± 0.22, 1.91 ± 0.22 and 3.03 ± 0.28 μM, respectively. Whereas, the IC50 values of Isotetrandrine against the above immune cells were 2.19 ± 0.27, 2.28 ± 0.33, 1.29 ± 0.14 and 1.55 ± 0.26 μM, respectively. The inhibitory effect of Isotetrandrine against the proliferation of T cells was stronger than that of tetrandrine significantly (p < 0.05). Molecular mechanism investigation showed that 10 μM of Isotetrandrine largely decreased the expression of p-NF-κB and NF-κB in both MOLT-4 and MOLT-4/DNR T cells (p < 0.05), whereas 10 μM of tetrandrine slightly inhibited the phosphorylation of p-NF-κB with little influence on the expression of NF-κB. Taken together, absolute configurations of tetrandrine and Isotetrandrine are suggested to influence on their anti-proliferation effects in human T cells via different regulation of NF-κB.
A modular approach to the bisbenzylisoquinoline alkaloids tetrandrine and Isotetrandrine
Org Biomol Chem 2020 Apr 29;18(16):3047-3068.PMID:32091528DOI:10.1039/d0ob00078g.
An efficient racemic total synthesis of the bisbenzylisoquinoline alkaloids tetrandrine and Isotetrandrine in four different routes is reported herein. Key steps of the synthesis include N-acyl Pictet-Spengler condensations to access the tetrahydroisoquinoline moieties, as well as copper-catalyzed Ullmann couplings for diaryl ether formation. Starting from commercially available building blocks tetrandrine and Isotetrandrine are accessed in 12 steps. Depending on the sequence of the four central condensation steps, equimolar mixtures of both diastereomers or predominantly tetrandrine or its diastereomer Isotetrandrine are obtained. Through computational analysis we were able to rationalize the differences in the observed diastereomeric specificities.
Isotetrandrine Reduces Astrocyte Cytotoxicity in Neuromyelitis Optica by Blocking the Binding of NMO-IgG to Aquaporin 4
Neuroimmunomodulation 2016;23(2):98-108.PMID:27064690DOI:10.1159/000444530.
Objective: Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease that affects the optic nerves and spinal cord with no cure and no FDA-approved therapy. Research over the last decade revealed that the binding of NMO-IgG to the water channel protein astrocyte aquaporin 4 (AQP4) might be the primary cause of NMO pathogenesis. The purpose of this study was to identify potential blockers of NMO-IgG and AQP4 binding. Methods: We developed a two-step screening platform consisting of a reporter cell-based high-throughput screen assay and a cell viability-based assay. Purified NMO-IgG from NMO patient serum and transfected Chinese hamster lung fibroblast V79 cells stably expressing human M23-AQP4 were used for primary screening of 40,000 small molecule fractions from 500 traditional Chinese herbs. Results: Thirty-six positive fractions were identified, of which 3 active fractions (at 50 μg/ml) were found to be from the same Chinese traditional herb Mahonia japonica (Thunb.). A bioactivity-guided method based on a primary screening assay for blocking activity led to the isolation of an active single natural compound, Isotetrandrine, from the 3 fractions. Our immunofluorescence staining results showed that Isotetrandrine can block NMO-IgG binding to AQP4 without affecting the expression and function of AQP4. It can also inhibit NMO-IgG binding to astrocyte AQP4 in NMO patient sera and block NMO-IgG-dependent complement-mediated cytotoxicity with the IC50 at ∼3 μM. Conclusions: The present study developed a cell-based high-throughput screen to identify small molecule inhibitors for NMO-IgG and AQP4 binding, and suggests a potential therapeutic value of Isotetrandrine in NMO.
In-vitro metabolism of Isotetrandrine, a bisbenzylisoquinoline alkaloid, in rat hepatic S9 fraction by high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry
J Pharm Pharmacol 2004 Jun;56(6):749-55.PMID:15231040DOI:10.1211/0022357023547.
The objective of this study was to investigate the in-vitro metabolism of Isotetrandrine, a bisbenzylisoquinoline alkaloid, using rat hepatic S9 fraction and to profile and identify its metabolites using high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry (HPLC-MS) and tandem mass spectrometry (MS/MS). Isotetrandrine was incubated at a concentration of 100 microg mL(-1) with male rat hepatic S9 fraction in the presence of an NADPH generating system (Tris buffer, pH 7.4, 37 degrees C). Samples were removed at 60 min after reaction initiation. Unchanged Isotetrandrine (approximately 63% of the sample) and four metabolites were profiled, characterized and tentatively identified using solvent extraction, methyl derivatization, and HPLC-MS and MS/MS techniques. Isotetrandrine metabolites were mainly formed via two main pathways, N-demethylation and isoquinoline ring oxidation. The first pathway produced a major metabolite, N-desmethyl Isotetrandrine (approximately 16% of the sample). The second pathway produced three minor oxidized metabolites, hydroxy-isotetrandrine (approximately 6% of the sample), oxo-isotetrandrine (approximately 7% of the sample), and oxohydroxy-isotetrandrine (approximately 7% of the sample). Diazomethane treatment of these metabolites did not produce any methyl derivatives and therefore the hydroxylated sites of the metabolites were tentatively assigned at the heterocyclic moieties of the isoquinoline rings. In conclusion, Isotetrandrine is substantially metabolized in this in-vitro rat hepatic system.